BMP8A sustains spermatogenesis by activating both SMAD1/5/8 and SMAD2/3 in spermatogonia.
Fang-Ju WuTing-Yu LinLi-Ying SungWei-Fang ChangPo-Chih WuChing-Wei LuoPublished in: Science signaling (2017)
Mutation in either of the genes encoding bone morphogenetic protein (BMP) 8A or 8B (Bmp8a or Bmp8b) causes postnatal depletion of spermatogonia in mice. We found that Bmp8a, but not Bmp8b, was expressed predominantly in the neonatal mouse spermatogonia. Although most BMPs induce activation of SMADs 1, 5, and 8 (SMAD1/5/8), but not SMADs 2 and 3 (SMAD2/3), we found that BMP8A induced signaling through both sets of transcription factors. In undifferentiated mouse spermatogonia, BMP8A activated SMAD1/5/8 through receptor complexes formed by ALK3 and either ACVR2A or BMPR2 and activated SMAD2/3 through receptor complexes formed by ALK5 and ACVR2A, ACVR2B, or TGFBR2. Signaling through SMAD2/3 promoted the proliferation of germ cells, whereas that through SMAD1/5/8 directed the subsequent differentiation of spermatogonia. BMP8A promoted spermatogenesis in cultured mouse testis explants, and the resulting spermatids were functionally competent for fertilization. These results suggest that the dual role of BMP8A in promoting proliferation and differentiation of spermatogonia may be exploited clinically to treat male infertility.
Keyphrases
- transforming growth factor
- mesenchymal stem cells
- epithelial mesenchymal transition
- bone regeneration
- signaling pathway
- transcription factor
- type diabetes
- cell proliferation
- adipose tissue
- genome wide
- advanced non small cell lung cancer
- gene expression
- cell death
- cell cycle arrest
- epidermal growth factor receptor
- genome wide identification
- genome wide analysis